The long-term goal of this research is to determine the role of the sensory and sympathetic limbs of the nervous system on the pathophysiology of interstitial cystitis (IC). IC is a painful, inflammatory bladder disease of human beings. The symptoms of IC (pain and increased urinary frequency and urgency) may be exacerbated by stressful experience. The cause(s) is (are) unknown. A significant impediment to progress in understanding IC has been the lack of an animal model of the disease. Using NIDDK grant DK 47537, the principal investigator has shown that the majority of cats presented to veterinarians for care of irritative voiding meet all of the objective criteria for diagnosis of IC in humans that can be applied to animals. Moreover, the natural history and pathophysiologic features are comparable in both species, making IC in cats an excellent spontaneously occurring disease model. This four year proposal is intended to use cats with IC to achieve the following objectives: 1) to determine if inhibiting sensory afferent neurons with capsaicin, or sympathetic efferent neurons with 6-hydroxydopamine, permits resolution of the clinical, bladder, and afferent, central and efferent nervous system abnormalities present in IC; 2) to determine the effects of IC and drug administration on in-vitro bladder strip contractility; and 3) to determine the long-term (6 month) effects of the drug that results in the greatest resolution of bladder abnormalities. The correlation of the clinical effects of these drugs with their effects on the bladder and nervous system should provide important new insights on the mechanisms underlying many of the abnormalities observed in patients with IC, and suggest more rational approaches to treatment of the disease than currently are available.